Diisopropylamine → HCID 178459330, compound

HRID 2423236Notes

Reaction equation

HRID 2423236 reaction equation
C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[Li+].CC([N-]C(C)C)C.[CH3:27][C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=1)=[O:29].Cl[S:38]([C:41]1[CH:42]=[C:43]([CH:47]=[CH:48][CH:49]=1)[C:44](Cl)=[O:45])(=[O:40])=[O:39].Cl.[OH:51][C:52]([CH3:57])([CH3:56])[C:53](=N)[NH2:54].[H-].[Na+].[Cl-].[NH4+:61]>C1COCC1>[F:36][C:32]1[CH:31]=[C:30]([C:28](=[O:29])[CH2:27][C:44]([C:43]2[CH:42]=[C:41]([S:38]([NH:61][C:53](=[NH:54])[C:52]([OH:51])([CH3:57])[CH3:56])(=[O:40])=[O:39])[CH:49]=[CH:48][CH:47]=2)=[O:45])[CH:35]=[CH:34][CH:33]=1

Participants

10

Reactant 8

HCID 7912DiisopropylamineHCID 99673-FluoroacetophenoneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 77671Benzoyl chloride, 3-(chlorosulfonyl)-HCID 2724682Lithium diisopropylamideHCID 426142842-Hydroxy-2-methylpropanimidamide hydrochlorideHCID 178418244HCID 178418244, compound

Product 1

HCID 178459330HCID 178459330, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1.58 M n-butyllithium/hexane solution (13.8 mL) was dropwise added to an anhydrous THF (30 mL) solution of diisopropylamine (3.08 mL) cooled to −78° C. under Ar gas atmosphere, thereby preparing a LDA solution. This solution was warmed up to −20° C., and then again cooled to −78° C., and thereafter 3-fluoroacetophenone (2.07 g) was dropwise added thereto, followed by stirring at −78° C. for 30 minutes. Then, 3-(chlorosulfonyl)benzoyl chloride (2.44 g) was dropwise added, followed by stirring for 15 minutes. Separately, 2-hydroxy-2-methylpropanimidamide hydrochloride (3.05 g) was added to a THF (40 mL) solution of sodium hydride (60% purity, 0.88 g) at room temperature, followed by stirring for 30 minutes and cooling to 0° C. Then, the previous solution was added thereto all at once, followed by stirring at room temperature for 1 hour. An aqueous saturated ammonium chloride solution was added, followed by extraction with ethyl acetate. The organic layer was washed with water, dried, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=50/1) to obtain N-({3-[3-(3-fluorophenyl)-3-oxopropanoyl]phenyl}sulfonyl)-2-hydroxy-2-methylpropanimidamide (2.17 g).

Workup

  1. temperatureThis solution was warmed up to −20° C.
  2. temperatureagain cooled to −78° C.
  3. stirringby stirring for 15 minutes
  4. stirringby stirring for 30 minutes
  5. temperaturecooling to 0° C
  6. additionThen, the previous solution was added
  7. stirringby stirring at room temperature for 1 hour
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layer was washed with water
  10. customdried
  11. customevaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (chloroform/methanol=50/1)

Sources & evidence

ORD record
ord-3a509b8f50654e72bcd0d9db7e6cdc28
Source dataset
uspto-grants-2011_06
Patent number
US07960562B2

Reaction notes

Loading…